Recombinant phospholipase A 2 inhibitor of Sinonatrix annularis (ringed water snake) attenuates hemorrhagic action of the venom from Daboia siamensis (Siamese Russell’s viper)

Abstract Background Phospholipase A 2 (PLA 2 ) is a common enzyme in snake venoms from many species that hydrolyzes phospholipids in cell membranes, causing local and systemic adverse effects. Interestingly, PLA 2 inhibitors in the snake blood are a natural neutralization against PLA 2 that is leaked into the circulation. Hence, synthesizing liver PLA 2 inhibitors might be a novel and effective anti-venom strategy. Objective To test if PLA 2 inhibitor gamma form (PLIϒ) reduces the hemorrhagic effect of crude Daboia siamensis (D. siamensis ) (a venomous viper with high PLA 2 abundance in the venom). Methods PLIϒ was synthesized and purified from the data of Sinonatrix annularis . Then, PLA 2 activity in the snake venoms was screened and tested against PLA 2 activity from crude D. siamensis venom. The hemorrhage effect of crude D. siamensis was measured with the minimum hemorrhagic activity dose in mice with and without PLIϒ. Results D. siamensis had the highest PLA 2 activity among the 5 selected venomous snakes. The PLIϒ reduced the PLA 2 activity of crude D. siamensis by up to 34.8% ( in vitro ) and decreased hemorrhagic spots in mice by up to 30.2% on the inner surface of mouse skins compared with controls. Conclusion PLIϒ reduced PLA 2 activity and was effective in mitigating the hemorrhagic effect of crude D. siamensis .